华西口腔医学杂志 ›› 2021, Vol. 39 ›› Issue (6): 642-650.doi: 10.7518/hxkq.2021.06.004

• 基础研究 • 上一篇    下一篇

2型糖尿病对小鼠下颌骨骨再生及辅助性T细胞17、调节性T细胞相关因子表达的影响

王亚楠1(), 吴旋2, 贾婷婷1, 冯瑶1, 刘世岳3, 徐欣1, 张东姣1()   

  1. 1.山东大学齐鲁医学院口腔医学院·口腔医院种植科 山东省口腔组织再生重点实验室 山东省口腔生物材料与组织再生工程实验室,济南 250012
    2.宁波口腔医院月湖分院种植科,宁波 315000
    3.山东大学齐鲁医学院口腔医学院·口腔医院牙周科 山东省口腔组织再生重点实验室 山东省口腔生物材料与组织再生工程实验室,济南 250012
  • 收稿日期:2020-12-25 修回日期:2021-09-14 出版日期:2021-12-01 发布日期:2021-12-03
  • 通讯作者: 张东姣 E-mail:wangyanan3045@163.com;djzhang1109@163.com
  • 作者简介:王亚楠,博士,E-mail:wangyanan3045@163.com
  • 基金资助:
    国家自然科学基金(82071148);泰山学者建设工程专项经费(TS201511106);国家重点研发计划(2016-YFC1102705);山东省自然科学基金(ZR2020QH158);中国博士后科学基金(2019M662371);山东大学口腔医院青年科研基金(2019QNJJ03)

Effect of type 2 diabetes mellitus on mandibular bone regeneration and the expression of T helper cell 17/regulat-ory T cell-related factors in mice

Wang Yanan1(), Wu Xuan2, Jia Tingting1, Feng Yao1, Liu Shiyue3, Xu Xin1, Zhang Dongjiao1()   

  1. 1.Dept. of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China
    2.Dept. of Implantology, Yuehu Branch, Ningbo Dental Hospital, Ningbo 315000, China
    3.Dept. of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China
  • Received:2020-12-25 Revised:2021-09-14 Online:2021-12-01 Published:2021-12-03
  • Contact: Zhang Dongjiao E-mail:wangyanan3045@163.com;djzhang1109@163.com
  • Supported by:
    National Natural Science Foundation of China(82071148);Construction Engineering Special Fund of Taishan Scholars(TS201511106);Key Project of Chinese National Programs for Research and Development(2016YFC1102705);Natural Science Foundation of Shandong Province(ZR2020QH158);China Postdoctoral Science Foundation(2019M662371);Youth Scientific Research Funds of School of Stomatology, Shandong University(2019QNJJ03)

摘要: 目的

观察2型糖尿病对小鼠下颌骨骨再生以及辅助性T细胞17(Th17)、调节性T细胞(Treg)相关因子表达的影响。

方法

将36只6周龄C57BL/6J雄性小鼠随机分为正常对照(NC)组和2型糖尿病(T2DM)组,小鼠下颌骨缺损建模当天(0 d)和术后7、14、28 d检测空腹血糖。于两组小鼠下颌骨缺损建模后7、14、28 d,通过苏木素-伊红(HE)染色观察下颌骨缺损愈合情况,通过免疫组织化学染色的方法观察下颌骨缺损内碱性磷酸酶(ALP)、Runt相关转录因子2(RUNX2)、叉头框蛋白P3(Foxp3)、维甲酸相关孤核受体γt(RORγt)和蛋白酪氨酸磷酸酶非受体型2(PTPN2)的表达情况。

结果

HE染色结果显示:T2DM组小鼠的下颌骨缺损范围内新生骨的数量明显少于NC组。免疫组织化学染色结果显示:成骨相关蛋白ALP和RUNX2的表达在T2DM组的骨缺损内明显降低;另外,2型糖尿病小鼠下颌骨缺损范围内的RORγt阳性细胞数量增加,Foxp3阳性细胞数量减少,PTPN2的表达明显降低。

结论

2型糖尿病可以显著地抑制小鼠下颌骨骨再生过程,PTPN2的下降以及Treg-Th17向偏移可能为其潜在的分子机制。

关键词: 2型糖尿病, 骨再生, 辅助性T细胞17, 调节性T细胞, 蛋白酪氨酸磷酸酶非受体型2

Abstract: Objective

To observe the effect of type 2 diabetes mellitus (T2DM) on mandibular bone regeneration and the expression of factors related to T helper cell 17 (Th17 cell) and regulatory T cell (Treg cell) in mice.

Methods

Thirty-six 6-week-old C57BL/6J male mice were randomly divided into normal control (NC) and T2DM groups. Fasting blood glucose levels were detected 0 d, 7 d, 14 d, and 28 d after surgery for mandibular defects. Hematoxylin-eosin (HE) staining was used in observing the bone after 7 d, 14 d, and 28 d of the healing process. Immunohistochemical staining was used in observing the expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), forkhead box protein P3 (Foxp3), retinoic acid related orphan receptor gamma T (RORγt), and protein tyrosine phosphatase non-receptor type 2 (PTPN2) after 7 d, 14 d, and 28 d of healing.

Results

HE staining showed that the area with new bones in the T2DM group was significantly smaller than that in the NC group. Immunohistochemical staining showed that the expression of osteogenesis related proteins ALP and RUNX2 were significantly reduced in the T2DM group. In addition, the number of RORγt positive cells increased, whereas the number of Foxp3 positive cells and the expression PTPN2 decreased significantly in the mandibular bone defect in mice with T2DM.

Conclusion

T2DM significantly inhibit mandibular bone regeneration in mice. Decline in PTPN2 expression and the transition of Treg and Th17 may be the underlying molecular mechanisms.

Key words: type 2 diabetes mellitus, bone regeneration, T helper cell 17, regulatory T cell, protein tyrosine phosphatase non-receptor type 2

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